Histone acetyltransferase Kat2a regulates ferroptosis via enhancing Tfrc and Hmox1 expression in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a prevalent myocardial microvascular complication of the myocardium with a complex pathogenesis. Investigating the pathogenesis of DCM can significantly contribute to enhancing its prevention and treatment strategies. Our study revealed an upregulation of lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by a decrease in N6-methyladenosine (m6A) modified Kat2a mRNA levels. Our study revealed an upregulation of lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by a decrease in N6-methyladenosine (m6A) modified Kat2a mRNA levels. Functionally, inhibition of Kat2a effectively ameliorated high glucose-induced cardiomyocyte injury both in vitro and in vivo by suppressing ferroptosis. Mechanistically, Demethylase alkB homolog 5 (Alkbh5) was found to reduce m6A methylation levels on Kat2a mRNA, leading to its upregulation. YTH domain family 2 (Ythdf2) played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and Hmox1 expression via enhancing the enrichment of H3K27ac and H3K9ac on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions.

High-density lipoprotein mimetic nano-therapeutics targeting monocytes and macrophages for improved cardiovascular care: a comprehensive review.

The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.

Numerical study and orthogonal analysis of optimal performance parameters for vertical cooling of sintered ore.

The sinter cooler, essential for cooling hot sintered ore to a specific temperature, has seen recent advancements with the introduction of a vertical sinter cooling furnace. This innovation aims to enhance energy efficiency, reduce emissions, and improve waste heat recovery. Despite significant research, a quantitative analysis of factors impacting its cooling and heat transfer efficiency is lacking. This study utilizes the Euler model and local non-equilibrium thermodynamic theory to identify key factors affecting the gas-solid cooperative cooling process in the vertical cooler. Through an orthogonal experimental approach, the paper determines the optimal structural and operational parameters for the furnace. Key findings include that a gas-solid ratio of 1200m^3/t, inlet air temperature of 50 â„ƒ, cooling section height of 6m, and diameter of 13.25m maximize efficiency, achieving a weighted range normalization value of 0.962. This configuration meets sintered ore cooling requirements while optimizing waste heat recovery. The study reveals that the impact on heat transfer efficiency is influenced primarily by the gas-solid ratio, followed by the cooling section's height, diameter, and inlet air temperature. These insights are crucial for enhancing the vertical sinter cooler's design, contributing to more energy-efficient and environmentally friendly sintering processes.

Ginsenoside RG1-induced mesenchymal stem cells alleviate diabetic cardiomyopathy through secreting exosomal circNOTCH1 to promote macrophage M2 polarization.

Diabetic cardiomyopathy (DCM) is a cardiac complication resulting from long-term uncontrolled diabetes, characterized by myocardial fibrosis and abnormal cardiac function. This study aimed at investigating the potential of ginsenoside RG1 (RG1)-induced mesenchymal stem cells (MSCs) in alleviating DCM. A DCM mouse model was constructed, and the effects of RG1-induced MSCs on myocardial function and fibrosis in diabetic mice were evaluated. RG1-induced MSCs were cocultured with high glucose-treated fibroblasts for subsequent functional and mechanism assays. It was discovered that RG1-induced MSCs secrete exosomes that induce macrophage M2 polarization. Mechanistically, exosomes derived from RG1-induced MSCs transferred circNOTCH1 into macrophages, activating the NOTCH signaling pathway. A competing endogenous RNA (ceRNA) regulatory axis consisting of circNOTCH1, miR-495-3p, and NOTCH1 was found to contribute to DCM alleviation.. This study unveiled that exosomal circNOTCH1 secreted by RG1-induced MSCs can alleviate DCM by activating the NOTCH signaling pathway to induce macrophage M2 polarization. This finding may contribute to the development of new therapeutic approaches for DCM.

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies.

OBJECTIVES: As a novel type of theta burst stimulation (TBS), continuous TBS (cTBS) has been shown to have mixed therapeutic effects for major depressive disorder (MDD) or bipolar depression (BD). Thus, we performed a meta-analysis of randomized controlled trials (RCTs) of cTBS for treating major depressive episodes in patients with MDD or BD. METHODS: A systematic search of four major bibliographic databases (PubMed, EMBASE, Cochrane Library, and PsycINFO) was conducted from inception dates to February 3, 2023 to identify eligible studies. The data were analyzed using a random-effects model. RESULTS: Three RCTs (n = 78, active cTBS = 37 and sham cTBS = 41) were included the meta-analysis. No significant differences were found in terms of change in Hamilton Depression Rating Scale (HAMD) scores (3 RCTs, n = 78, SMD = -0.09, 95 % CI: -0.53 to 0.36; I2 = 0 %; P = 0.71) and study-defined response (2 RCTs, n = 58, 26.7 % versus 21.4 %, RR = 1.20, 95 % CI: 0.48 to 2.96; I2 = 0 %; P = 0.70) between active and sham cTBS groups. Similarly, no group differences were found in the rates of adverse events and discontinuation due to any reason (P > 0.05). LIMITATIONS: Meta-analysis had small sample sizes and low number of included studies. CONCLUSIONS: Although cTBS appeared to be a safe and well-tolerated option for treating major depressive episodes in MDD or BD patients, no advantage in treatment effects was found in this meta-analysis. Future large-scale studies are warranted to assess the efficacy of cTBS for MDD or BD patients with a major depressive episode.

Factors influencing the mental health status of support nurses and their workload during the COVID-19 epidemic.

OBJECTIVES: The authors used the National Aeronautics and Space Administration Task Load Index (NASA-TLX) and general health questionnaire to analyze the factors influencing the mental health status and the workload of support nurses during the COVID-19 epidemic. MATERIAL AND METHODS: The authors conducted a cross-sectional survey of 349 support nurses in April-October 2022. Using QuestionStar, a powerful online survey tool, the authors administered surveys to the participants, collected data on the mental health status and workload of support nurses, and analyzed the influencing factors based on the collected data. RESULTS: A total of 316 questionnaires were successfully collected, with an effective rate of 98.75%. The proportion of support nurses with mental health problems was 25% and the value of the NASA-TLX questionnaire was: M±SD 68.91±7.28 pts. Multi-factor analysis revealed that the number of children, family support, and nursing support location were the influencing factors of mental health status, while the multivariate analysis revealed that the presence of symptoms, nursing support location, support work type, and total 12-item General Health Questionnaire (GHQ-12) score were the influencing factors of the workload of support nurses. CONCLUSIONS: Compared to their counterparts in the plains, nurses working in isolated plateau regions who were caring for children and lacked family support, were more likely to have mental health issues. There was a positive correlation between the changes in GHQ-12 and NASA-TLX scores of the study participants. Compared to their counterparts in the plains and the tropical regions, nurses working in plateau regions had a heavier workload. As part of the follow-up measures to prevent and treat patients impacted by the COVID-19 epidemic, it is important to improve the mental health evaluation, consultation, and treatment of the support nurses to guarantee the high quality of the first-line support work. Int J Occup Med Environ Health. 2023;36(6)761-72.

Chemokine receptor CXCR2 in primary sensory neurons of trigeminal ganglion mediates orofacial itch.

The CXCR2 chemokine receptor is known to have a significant impact on the initiation and control of inflammatory processes. However, its specific involvement in the sensation of itch is not yet fully understood. In this study, we aimed to elucidate the function of CXCR2 in the trigeminal ganglion (TG) by utilizing orofacial itch models induced by incision, chloroquine (CQ), and histamine. Our results revealed a significant up-regulation of CXCR2 mRNA and protein expressions in the primary sensory neurons of TG in response to itch stimuli. The CXCR2 inhibitor SB225002 resulted in notable decrease in CXCR2 protein expression and reduction in scratch behaviors. Distal infraorbital nerve (DION) microinjection of a specific shRNA virus inhibited CXCR2 expression in TG neurons and reversed itch behaviors. Additionally, the administration of the PI3K inhibitor LY294002 resulted in a decrease in the expressions of p-Akt, Akt, and CXCR2 in TG neurons, thereby mitigating pruritic behaviors. Collectively, we report that CXCR2 in the primary sensory neurons of trigeminal ganglion contributes to orofacial itch through the PI3K/Akt signaling pathway. These observations highlight the potential of molecules involved in the regulation of CXCR2 as viable therapeutic targets for the treatment of itch.

Bilateral theta burst stimulation for patients with acute unipolar or bipolar depressive episodes: A systematic review of randomized controlled studies.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluated the overall efficacy and safety of bilateral theta-burst stimulation (TBS) as an intervention for patients with mood disorders. METHODS: A systematic search (up to December 7, 2022) of RCTs was conducted to address the study aims. A random-effects meta-analysis was performed by including study-defined responses and remission as primary outcomes. RESULTS: Analyses included six RCTs comprising 285 participants with major depressive disorder (MDD) (n = 233) or a depressive episode in the course of bipolar disorder (BD) (n = 52) who had undergone active bilateral TBS (n = 142) versus sham stimulation (n = 143). Active bilateral TBS outperformed sham stimulation with respect to study-defined improvements (55.1 % versus 20.3 %, 4 RCTs, n = 152, 95%CI: 1.63 to 4.39, P < 0.0001; I2 = 0 %) and remission rates (37.2 % versus 14.3 %, 2 RCTs, n = 85, 95%CI: 1.13 to 5.95, P = 0.02; I2 = 0 %) in MDD patients but not those with bipolar or unipolar mixed depression. Superiority of active bilateral TBS over sham stimulation was confirmed for improvements in depressive symptoms at post-bilateral TBS assessments and 8-week follow-ups in patients with either MDD or mixed depression (all P < 0.05). Discontinuation rates due to any reason and adverse events (i.e., headache, dizziness) were similar between TBS and sham stimulation groups with MDD or mixed depression (all P > 0.05). CONCLUSION: Bilateral TBS targeting the dorsolateral prefrontal cortex (DLPFC) appears to be a well-tolerated form of repetitive transcranial magnetic stimulation (rTMS) that has substantial antidepressant effects, particularly in patients with MDD. Effects of bilateral TBS on bipolar and unipolar mixed depression should be further investigated.

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review.

Objective: Intermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment-resistant depression (TRD). Methods: Randomized controlled trials (RCTs) comparing the efficacy and safety of iTBS and HF-rTMS were identified by searching English and Chinese databases. The primary outcomes were study-defined response and remission. Results: Two RCTs (n = 474) investigating the efficacy and safety of adjunctive iTBS (n = 239) versus HF-rTMS (n = 235) for adult patients with TRD met the inclusion criteria. Among the two included studies (Jadad score = 5), all were classified as high quality. No group differences were found regarding the overall rates of response (iTBS group: 48.0% versus HF-rTMS group: 45.5%) and remission (iTBS group: 30.0% versus HF-rTMS group: 25.2%; all Ps > 0.05). The rates of discontinuation and adverse events such as headache were similar between the two groups (all Ps > 0.05). Conclusion: The antidepressant effects and safety of iTBS and HF-rTMS appeared to be similar for patients with TRD, although additional RCTs with rigorous methodology are needed.

Accelerated intermittent theta burst stimulation for major depressive disorder or bipolar depression: A systematic review and meta-analysis.

We aimed to systematically evaluate the clinical efficacy and safety of accelerated intermittent theta burst stimulation (aiTBS) for patients with major depressive disorder (MDD) or bipolar depression (BD). A random-effects model was adopted to analyze the primary and secondary outcomes using the Review Manager, Version 5.3 software. This meta-analysis (MA) identified five double-blind randomized controlled trials (RCTs) comprising 239 MDD or BD patients with a major depressive episode. Active aiTBS overperformed sham stimulation in the study-defined response. This MA found preliminary evidence that active aiTBS resulted in a greater response in treating major depressive episodes in MDD or BD patients than sham stimulation.

Low-frequency repetitive transcranial magnetic stimulation for children and adolescents with first-episode and drug-naïve major depressive disorder: A systematic review.

Objective: This systematic review of randomized controlled trials (RCTs) was conducted to explore the therapeutic effects and safety of active low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) versus sham LF-rTMS in children and adolescent patients with first-episode and drug-naïve (FEDN) major depressive disorder (MDD). Methods: A systematic literature search was performed, and data were extracted by two independent researchers. The coprimary outcomes were study-defined response and remission. Results: A systematic search of the literature yielded 442 references, of which 3 RCTs (130 children and adolescents with FEDN MDD, 50.8% male, and mean age range from 14.5 to 17.5 years) met the inclusion criteria. Among the two RCTs (66.7%, 2/3) examining the effects of LF-rTMS on study-defined response and remission and cognitive function, active LF-rTMS was more efficacious than sham LF-rTMS in terms of study-defined response rate and cognitive function (all p < 0.05) but not regarding study-defined remission rate (all p > 0.05). No significant group differences were found with regard to adverse reactions. None of the included RCTs reported the dropout rate. Conclusion: These findings preliminarily found that LF-rTMS could benefit children and adolescents with FEDN MDD in a relatively safe manner, although further studies are warranted.

Stanford neuromodulation therapy for treatment-resistant depression: a systematic review.

Objective: This systematic review of randomized controlled studies (RCTs) and observational studies evaluated the efficacy and safety of stanford neuromodulation therapy (SNT) for patients with treatment-resistant depression (TRD). Methods: A systematic search (up to 25 September, 2023) of RCTs and single-arm prospective studies was conducted. Results: One RCT (n = 29) and three single-arm prospective studies (n = 34) met the study entry criteria. In the RCT, compared to sham, active SNT was significantly associated with higher rates of antidepressant response (71.4% versus 13.3%) and remission (57.1% versus 0%). Two out of the three single-arm prospective studies reported the percentage of antidepressant response after completing SNT, ranging from 83.3% (5/6) to 90.5% (19/21). In the three single-arm prospective studies, the antidepressant remission rates ranged from 66.7% (4/6) to 90.5% (19/21). No severe adverse events occurred in all the four studies. Conclusion: This systematic review found SNT significantly improved depressive symptoms in patients with TRD within 5 days, without severe adverse events.

Transcranial alternating current stimulation for schizophrenia: a systematic review of randomized controlled studies.

Background: In randomized clinical trials (RCTs) investigating the application of transcranial alternating current stimulation (tACS) in schizophrenia, inconsistent results have been reported. The purpose of this exploratory systematic review of RCTs was to evaluate tACS as an adjunct treatment for patients with schizophrenia based on its therapeutic effects, tolerability, and safety. Methods: Our analysis included RCTs that evaluated adjunctive tACS' effectiveness, tolerability, and safety in schizophrenia patients. Three independent authors extracted data and synthesized it using RevMan 5.3 software. Results: Three RCTs involving 76 patients with schizophrenia were encompassed in the analysis, with 40 participants receiving active tACS and 36 receiving sham tACS. Our study revealed a significant superiority of active tACS over sham tACS in improving total psychopathology (standardized mean difference [SMD] = -0.61, 95% confidence interval [CI]: -1.12, -0.10; I2 = 16%, p = 0.02) and negative psychopathology (SMD = -0.65, 95% CI: -1.11, -0.18; I2 = 0%, p = 0.007) in schizophrenia. The two groups, however, showed no significant differences in positive psychopathology, general psychopathology, or auditory hallucinations (all p > 0.05). Two RCTs examined the neurocognitive effects of tACS, yielding varied findings. Both groups demonstrated similar rates of discontinuation due to any reason and adverse events (all p > 0.05). Conclusion: Adjunctive tACS is promising as a viable approach for mitigating total and negative psychopathology in individuals diagnosed with schizophrenia. However, to gain a more comprehensive understanding of tACS's therapeutic effects in schizophrenia, it is imperative to conduct extensive, meticulously planned, and well-documented RCTs.

Exogenous Calcium Suppresses the Oviposition Choices of Frankliniella occidentalis (Thysanoptera: Thripidae) and Promotes the Attraction of Orius similis (Hemiptera: Anthocoridae) by Altering Volatile Blend Emissions in Kidney Bean Plants.

Frankliniella occidentalis is a destructive pest of horticultural plants, while Orius similis is a natural enemy of thrips. It has been demonstrated that exogenous calcium could induce plant defenses against herbivore attack. We examined whether CaCl2 supplementation altered the volatile emissions of kidney bean plants, which influence the oviposition preference of F. occidentalis. We also assessed the influence of volatile cues on O. similis. Using Y-tube olfactometer tests, we found that exogenous CaCl2 treatment inhibited the selectivity of F. occidentalis but attracted O. similis. In addition, CaCl2 treatment reduced the oviposition preference of F. occidentalis. Gas chromatography-mass spectrometry analyses revealed that CaCl2 treatment altered the number and relative abundance of the volatile compounds in kidney bean plants and that (E)-2-hexen-1-ol, 1-octen-3-ol, ß-lonone, and (E,E)-2,4-hexadienal might be potential olfactory cues. Furthermore, the results of the six-arm olfactometer test indicated that 1-octen-3-ol (10-2 µL/µL), ß-lonone (10-2 µL/µL), and (E,E)-2,4-hexadienal (10-3 µL/µL) repelled F. occidentalis but attracted O. similis. Overall, our results suggested that exogenous CaCl2 treatment induced defense responses in kidney bean plants, suggesting that CaCl2 supplementation may be a promising strategy to enhance the biological control of F. occidentalis.

Application of continuous nursing care based on hierarchical diagnosis and treatment mode in Stage II cardiac rehabilitation of patients after percutaneous coronary intervention.

Objective: To explore the effect of applying continuous nursing care based on hierarchical diagnosis and treatment in Stage II cardiac rehabilitation of patients after percutaneous coronary intervention (PCI) and provide a theoretical basis for clinical nursing intervention. Methods: Patients in PCI postoperative II cardiac rehabilitation were selected and randomly divided into the experimental group (community group), the experimental group (rehabilitation group), and the control group. Patients in the control group received the routine cardiac rehabilitation management scheme, while those in the experimental groups received continuous nursing protocol based on the hierarchical diagnosis and treatment mode. All patients were compared for the cardiac rehabilitation evaluation indexes at discharge and 6 months after discharge. Results: Compared with the control group, the left ventricular ejection fraction, 6-minute walking distance test, medication compliance, and quality of life were all improved in the two experimental groups, and the differences were statistically significant (P < 0.05). The improvement in the rehabilitation group was more significant than in the community group. There were more patients with high cardiac rehabilitation compliance in the rehabilitation group than in the community group, with the difference being statistically significant (P < 0.05). Conclusion: Continuous nursing care rehabilitation based on the hierarchical diagnosis and treatment mode can improve the cardiac function of patients after PCI, enhance their quality of life, and improve their rehabilitation and medication compliance, facilitating their cardiac rehabilitation.

MED27, SLC6A7, and MPPE1 Variants in a Complex Neurodevelopmental Disorder with Severe Dystonia.

BACKGROUND: Despite advances in next generation sequencing technologies, the identification of variants of uncertain significance (VUS) can often hinder definitive diagnosis in patients with complex neurodevelopmental disorders. OBJECTIVE: The objective of this study was to identify and characterize the underlying cause of disease in a family with two children with severe developmental delay associated with generalized dystonia and episodic status dystonicus, chorea, epilepsy, and cataracts. METHODS: Candidate genes identified by autozygosity mapping and whole-exome sequencing were characterized using cellular and vertebrate model systems. RESULTS: Homozygous variants were found in three candidate genes: MED27, SLC6A7, and MPPE1. Although the patients had features of MED27-related disorder, the SLC6A7 and MPPE1 variants were functionally investigated. SLC6A7 variant in vitro overexpression caused decreased proline transport as a result of reduced cell-surface expression, and zebrafish knockdown of slc6a7 exhibited developmental delay and fragile motor neuron morphology that could not be rescued by L-proline transporter-G396S RNA. Lastly, patient fibroblasts displayed reduced cell-surface expression of glycophosphatidylinositol-anchored proteins linked to MPPE1 dysfunction. CONCLUSIONS: We report a family harboring a homozygous MED27 variant with additional loss-of-function SLC6A7 and MPPE1 gene variants, which potentially contribute to a blended phenotype caused by multilocus pathogenic variants. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Fabrication of apigenin nanoparticles using antisolvent crystallization technology: A comparison of supercritical antisolvent, ultrasonic-assisted liquid antisolvent, and high-pressure homogenization technologies.

Flavonoids have many positive pharmacological properties, such as antioxidant, antitumor, and anti-inflammatory activities. However, factors such as low water solubility and low dissolution rate limit their use. To overcome their poor solubility, carrier-free apigenin (API) microparticles and nanoparticles were prepared using three types of antisolvent precipitation technologies: supercritical antisolvent (SCF) technology, ultrasonic-assisted liquid antisolvent (UAL) technology, and high-pressure homogenization (HPH) technology. All three technologies can produce uniform tiny particles. However, the API particles obtained using these different techniques show subtle differences in terms of physical and chemical properties and biological activity. The preparation, characterization, and potential use of API microparticles and nanoparticles to improve in vitro release were studied. The resulting API particles were investigated and compared using Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. We determined the optimum conditions for SCF, UAL, and HPH technologies to produce API microparticles and nanoparticles. The antioxidant and antitumor properties of the API particles were also investigated. The results demonstrated that the reduced particle size of the APIs prepared via SCF, UAL, and HPH technologies contributed to the enhanced dissolution rate, which in turn enhanced API bioactivity.

Inhibitions and Down-Regulation of Motor Protein Eg5 Expression in Primary Sensory Neurons Reveal a Novel Therapeutic Target for Pathological Pain.

The motor protein Eg5, known as kif11 or kinesin-5, interacts with adjacent microtubules in the mitotic spindle and plays essential roles in cell division, yet the function of Eg5 in mature postmitotic neurons remains largely unknown. In this study, we investigated the contribution and molecular mechanism of Eg5 in pathological pain. Pharmacological inhibition of Eg5 and a specific shRNA-expressing viral vector reversed complete Freund's adjuvant (CFA)-induced pain and abrogated vanilloid receptor subtype 1 (VR1) expression in dorsal root ganglion (DRG) neurons. In the dorsal root, Eg5 inhibition promoted VR1 axonal transport and decreased VR1 expression. In the spinal cord, Eg5 inhibition suppressed VR1 expression in axon terminals and impaired synapse formation in superficial laminae I/II. Finally, we showed that Eg5 is necessary for PI3K/Akt signalling-mediated VR1 membrane trafficking and pathological pain. The present study provides compelling evidence of a noncanonical function of Eg5 in primary sensory neurons. These results suggest that Eg5 may be a potential therapeutic target for intractable pain.